Effects of a functional COMT polymorphism on brain anatomy and cognitive function in adults with velo-cardio-facial syndrome

<jats:sec id="S0033291707000700_sec_a001"><jats:title>Background</jats:title><jats:p>Velo-cardio-facial syndrome (VCFS) is associated with deletions at chromosome 22q11, abnormalities in brain anatomy and function, and schizophrenia-like psychosis. Thus it is assumed that one or more genes within the deleted region are crucial to brain development. However, relatively little is known about how genetic variation at 22q11 affects brain structure and function. One gene on 22q11 is catechol-O-methyltransferase (COMT): an enzyme that degrades dopamine and contains a functional polymorphism (<jats:italic>Val</jats:italic><jats:sup><jats:italic>158</jats:italic></jats:sup><jats:italic>Met</jats:italic>) affecting enzyme activity. Here, we investigated the effect of COMT <jats:italic>Val</jats:italic><jats:sup><jats:italic>158</jats:italic></jats:sup><jats:italic>Met</jats:italic> polymorphism on brain anatomy and cognition in adults with VCFS.</jats:p></jats:sec><jats:sec id="S0033291707000700_sec_a002"><jats:title>Method</jats:title><jats:p>The COMT <jats:italic>Val</jats:italic><jats:sup><jats:italic>158</jats:italic></jats:sup><jats:italic>Met</jats:italic> polymorphism was genotyped for 26 adults with VCFS on whom DNA was available. We explored its effects on regional brain volumes using hand tracing approaches; on regional grey- and white-matter density using computerized voxel-based analyses; and measures of attention, IQ, memory, executive and visuospatial function using a comprehensive neuropsychological test battery.</jats:p></jats:sec><jats:sec id="S0033291707000700_sec_a003" sec-type="results"><jats:title>Results</jats:title><jats:p>After corrections for multiple comparisons <jats:italic>Val</jats:italic>-hemizygous subjects, compared with <jats:italic>Met</jats:italic>-hemizygotes, had a significantly larger volume of frontal lobes. Also, <jats:italic>Val</jats:italic>-hemizygotes had significantly increased grey matter density in cerebellum, brainstem, and parahippocampal gyrus, and decreased white matter density in the cerebellum. No significant effects of COMT genotype on neurocognitive performance were found.</jats:p></jats:sec><jats:sec id="S0033291707000700_sec_a004" sec-type="conclusion"><jats:title>Conclusions</jats:title><jats:p>COMT genotype effects on brain anatomy in VCFS are not limited to frontal regions but also involve other structures previously implicated in VCFS. This suggests variation in COMT activity is implicated in brain development in VCFS.</jats:p></jats:sec>